Evidence map›Paper›PMID 30579042›Full record

ArticleMolecular therapy. Nucleic acids2019

Proximity Ligation Assays for In Situ Detection of Innate Immune Activation: Focus on In Vitro-Transcribed mRNA.

Emmeline L Blanchard, Kristin H Loomis, Sushma M Bhosle, Daryll Vanover, Patrick Baumhof, Bruno Pitard, Chiara Zurla, Philip J Santangelo

Abstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Phosphatase, MgHaematologica · 2024
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action.Current topics in microbiology and immunology · 2022
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Emmeline L BlanchardWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA.
Kristin H LoomisWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA.
Sushma M BhosleWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA.
Daryll VanoverWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA.
Patrick BaumhofCureVac, Paul-Ehrlich-Straße 15, 72076 Tübingen, Germany.
Bruno PitardIn-Cell-Art, 21 rue de la Noue Bras de Fer, 44200 Nantes, France.
Chiara ZurlaWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA.
Philip J SantangeloWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, UA Whitaker Building, Atlanta, GA 30332, USA. Electronic address: philip.santangelo@bme.gatech.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The characterization of innate immune activation is crucial for vaccine and therapeutic development, including RNA-based vaccines, a promising approach. Current measurement methods quantify type I interferon and inflammatory cytokine production, but they do not allow for the isolation of individual pathways, do not provide kinetic activation or spatial information within tissues, and cannot be translated into clinical studies. Here we demonstrated the use of proximity ligation assays (PLAs) to detect pattern recognition receptor (PRR) activation in cells and in tissue samples. First, we validated PLA's sensitivity and specificity using well-characterized soluble agonists. Next, we characterized PRR activation from in vitro-transcribed (IVT) mRNAs, as well as the effect of sequence and base modifications in vitro. Finally, we established the measurement of PRR activation in tissue sections via PLA upon IVT mRNA intramuscular (i.m.) injection in mice. Overall, our results indicate that PLA is a valuable, versatile, and sensitive tool to monitor PRR activation for vaccine, adjuvant, and therapeutic screening.

Indexed as

innate immune responsesin vitro-transcribed mRNAprotein-protein interactionsproximity ligation assay

Identifiers

PMID30579042
PMCPMC6304375

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.